A composition for preventing or treating an rna viral infection comprising samhd1 or a nucleic acid molecule encoding the samhd1

Abstract

The present disclosure relates to the ssRNA-specific ribonuclease activity of SAMHD1 (sterile alpha motif (SAM) domain and HD domain-containing protein 1) and its use. It is noteworthy that SAMHD1 has dual catalytic functions which are ribonuclease activity and dNTPase activity: however unlike the dNTPase activity, the ribonuclease activity of SAMHD1 did not require the cofactor dGTP. The present invention can be employed to degrade viral genomic ssRNA and to prevent or treat a ssRNA viral infection.

What is claimed is: 
     
         1 . A pharmaceutical composition for preventing or treating an RNA viral infection comprising a therapeutically effective amount of an RNA-degrading molecule as an active ingredient, wherein the RNA-degrading molecule is selected from SAMHD1 (SAM domain and HD domain-containing protein 1) and a nucleic acid molecule encoding the SAMHD1, and wherein the RNA virus is a single stranded RNA (ssRNA) virus selected from a group consisting of a retrovirus, a positive-sense ssRNA virus, a negative-sense ssRNA virus and an ambisense ssRNA virus. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the retrovirus is selected from a group consisting of Lentivirus, Alpharetrovirus, Betaretrovirus, Gamma retrovirus, Deltaretrovirus, Spumavirus and Epsilonretrovirus. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the retrovirus is selected from a group consisting of Human immunodeficiency virus, Simian immunodeficiency virus, Caprine arthritis encephalitis virus, Visna/maedi virus, Feline immunodeficiency virus, Puma lentivirus, Equine infectious anemia virus, Bovine immunodeficiency virus, Jembrana disease virus, Avian leukosis virus, Rous sarcoma virus, Jaagsiekte sheep retrovirus, Simian retrovirus, Mouse mammary tumor virus, Feline leukemia virus, Bovine leukemia virus, Walleye epidermal hyperplasia virus 1 and Walleye epidermal hyperplasia virus 2. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the positive-sense ssRNA virus is selected from a group consisting of Arteriviridae, Coronaviridae, Roniviridae, Dicistroviridae, Iflaviridae, Marnaviridae, Picornaviridae, Secoviridae, Alphaflexiviridae, Betaflexiviridae, Gammaflexiviridae, Tymoviridae, Astrovirus, Barnaviridae, Bromoviridae, Caliciviridae, Closteroviridae, Flaviviridae, Leviviridae, Luteoviridae, Narnaviridae, Nodaviridae, Potyviridae, Togaviridae, Tombusviridae, Virgaviridae, Benyvirus, Cilevirus, Hepevirus, Idaeovirus, Ourmiavirus, Sobemovirus and Umbravirus. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the positive-sense ssRNA virus is selected from a group consisting of Equine arteritis virus, Lactate dehydrogenase elevating virus, Porcine reproductive and respiratory syndrome virus, Simian hemorrhagic fever virus, Coronavirus, Severe acute respiratory syndrome (SARS) coronavirus, Cripavirus, Deformed wing virus, Poliovirus, Human rhinoviruses, Hepatitis A virus, Avian nephritis virus, Norwalk virus, Yellow fever virus, West Nile virus, Hepatitis C virus, Dengue fever virus, Barley yellow dwarf virus, Rubella virus, Ross River virus, Sindbis virus, Chikungunya virus, Hepatitis E virus, Beet necrotic yellow vein virus, Beet soil-borne mosaic virus, Cocksfoot mottle virus, Lucerne transient streak virus and Rice yellow mottle virus. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the negative-sense ssRNA virus is selected from a group consisting of Bornaviridae, Filoviridae, Paramyxoviridae, Rhabdoviridae, Arenaviridae, Bunyaviridae, Ophioviridae, Orthomyxoviridae, Deltavirus, Nyavirus and Tenuivirus. 
     
     
         7 . The pharmaceutical composition of  claim 6 , wherein the negative-sense ssRNA virus is selected from a group consisting of Borna disease virus, Ebola virus, Marburg virus, Measles virus, Mumps virus, Nipah virus, Hendra virus, Rabies virus, Lassa virus, Hantavirus, Citrus psorosis virus, Influenzavirus A, Influenzavirus B, Influenzavirus C and hepatitis D virus. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the ambisense ssRNA virus is Bunyaviridae or Arenaviridae. 
     
     
         9 . The pharmaceutical composition of  claim 8 , wherein the ambisense ssRNA virus is selected from a group consisting of Nairovirus, Orthobunyavirus, Phlebovirus, Tospovirus, Lymphocytic choriomeningitis (LCM) virus and Lassa fever virus. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the SAMHD1 is lack of dNTPase activity. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the SAMHD1 has the substitution mutation of Asn or Ala for Asp at position 137 of SEQ ID NO:17. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the RNA-degrading molecule is able to degrade viral genomic ssRNA without dGTP as a cofactor. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the SAMHD1-encoding nucleic acid molecule is operatively linked to a promoter in an expression cassette. 
     
     
         14 . The pharmaceutical composition of  claim 1 , wherein the RNA-degrading molecule is 3′-5′ exoribonuclease. 
     
     
         15 . The pharmaceutical composition of  claim 1 , wherein the RNA-degrading molecule degrades viral genomic ssRNA present in a cell cytoplasm. 
     
     
         16 . The pharmaceutical composition of  claim 1 , wherein ssRNAs of the RNA virus are degraded into 5 to 8-mer oligonucleotides by the RNA-degrading molecule. 
     
     
         17 . A composition for degrading a viral genomic ssRNA comprising an RNA-degrading molecule selected from SAMHD1 and a nucleic acid molecule encoding the SAMHD1, wherein the virus is selected from a group consisting of a retrovirus, a positive-sense ssRNA virus, a negative-sense ssRNA virus and an ambisense ssRNA virus. 
     
     
         18 . A method of preventing or treating an RNA viral infection in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising an RNA-degrading molecule selected from SAMHD1 and a nucleic acid molecule encoding the SAMHD1, wherein the RNA virus is a ssRNA virus selected from a group consisting of a retrovirus, a positive-sense ssRNA virus, a negative-sense ssRNA virus and an ambisense ssRNA virus. 
     
     
         19 . A method of degrading a viral genomic ssRNA in a cell infected by a ssRNA virus, comprising introducing to the cell an RNA-degrading molecule selected from SAMHD1 and a nucleic acid molecule encoding the SAMHD1, thereby degrading the viral genomic ssRNA, wherein the virus is selected from a group consisting of a retrovirus, a positive-sense ssRNA virus, a negative-sense ssRNA virus and an ambisense ssRNA virus. 
     
     
         20 . Use of SAMHD1 or a nucleic acid molecule encoding the SAMHD1 as an RNA-degrading molecule for preventing or treating an RNA viral infection, wherein the RNA virus is a ssRNA virus selected from a group consisting of a retrovirus, a positive-sense ssRNA virus, a negative-sense ssRNA virus and an ambisense ssRNA virus. 
     
     
         21 . Use of SAMHD1 or a nucleic acid molecule encoding the SAMHD1 as an RNA-degrading molecule for degrading a viral genomic ssRNA, wherein the virus is selected from a group consisting of a retrovirus, a positive-sense ssRNA virus, a negative-sense ssRNA virus and an ambisense ssRNA virus.